Hematopoietic Stem Cell Transplantation From Unrelated Donors in 2 Cases of Interleukin-10 Receptor Deficiency: Is Surgery Not a Requirement?

Mutations in interleukin-10 and its receptors cause infantile inflammatory bowel disease (IBD), a hyperinflammatory disorder characterized by severe, treatment-refractory colitis, multiple abscesses, and enterocutaneous fistulas. Patients with infantile IBD often require several surgical interventions, including complete colectomy, and hematopoietic stem cell transplantation is currently the only known medical therapy. Traditionally, operative management has been preferred before stem cell transplantation because of the latter's increased susceptibility to procedural complications; however, surgical intervention could be delayed, and possibly reconsidered, because our 2 patients with infantile IBD demonstrated a rapid response to treatment via engraftment.

Ingestion of Fireworks: Rare Cause of Poisoning in Children.

BACKGROUND: Mistaken ingestion of all manner of toxic matter is common in childhood, but poisoning with fireworks and matchsticks is rare. Fireworks usually contain 10% yellow phosphorus and 50% potassium chlorate. Potassium chlorate is an extremely reactive and toxic agent that is used in fireworks and matchstick heads. METHODS: Eleven cases (7 females and 5 males; median age, 36 months [ranging from 24 to 48 months]) of poisoning after ingestion of fireworks and matchstick(s), between February 2008 and June 2014, were reviewed. RESULTS: The most common initial symptom was vomiting except for 2 cases in this group. Biochemical tests indicated that hyperphosphatemia was present in all patients, 8 patients (72.7%) had subclinical hepatic injury, 1 (9%) had acute hepatic failure, and 2 patients had no clinical or biochemical evidence of hepatic damage. Three patients had renal impairment, but none of them required dialysis. All of the patients recovered with supportive therapy except for 2 cases. One patient underwent cadaveric liver transplantation, whereas the other died because of circulatory dysfunction and respiratory failure due to pulmonary alveolar hemorrhage. CONCLUSIONS: Without prompt intervention, poisoning with fireworks carries high morbidity and mortality in children. It can cause pulmonary hemorrhage, in addition to other organ damage, including liver and kidney. Hyperphosphatemia is common, as it was seen in all of the study patients.

The Effect of Enteral Nutrition Support Rich in TGF-ß in the Treatment of Inflammatory Bowel Disease in Childhood.

Background and Objective: Malnutrition is a major complication of inflammatory bowel disease (IBD). Our aim of the study was to examine the effects of Modulen IBD supplementation, which was administered to IBD patients without limiting their daily diet in addition to medical treatment, on the clinical, laboratory, anthropometric values, and disease activities of these patients. Materials and Methods: Seventy three children with IBD were evaluated retrospectively. The cases were classified as those who had Crohn disease receiving (CD-M; n = 16) or not receiving Modulen IBD (CD; n = 19) and those who had ulcerative colitis receiving (UC-M; n = 13) or not receiving Modulen IBD (UC; n = 25). Disease activities, laboratory values, remission rates, and anthropometric measurements of the groups were compared. In addition to IBD treatment, Modulen IBD in which half of the daily calorie requirement was provided was given for eight weeks. Results: In the third month of treatment, 14 (88%) patients were in remission in CD-M group and eight (42%) patients were in remission in CD group. The height and weight z scores, which were low at the time of diagnosis, improved in the first week in CD-M group. Inflammatory parameters (UC) were significantly lower in the UC-M group compared to the UC group in first and third months. In the third month, eight (62%) patients in the UC-M group and four (16%) in the UC group were remitted clinically and in terms of laboratory values. Conclusions: TGF-ß-rich enteral nutrition support in children with IBD is an easy, effective, and reliable approach. It was shown that TGF-ß-rich enteral nutritional supplementation enabled the disease to enter the remission earlier, and contributed to the early recovery of weight and height scores.

Essential thrombocythemia with Mpl W515 K mutation in a child presenting with Budd-Chiari syndrome.

Essential thrombocythemia (ET) is an extremely rare childhood disorder characterised by clonal expansion of megakaryocytic lineage in bone marrow, leading to a persistent increase in the number of circulating thrombocytes and thus increased risk for thrombotic and haemorrhagic events. The molecular mechanisms of ET are not fully understood. Most children with ET have the JAK2 V617F somatic mutation; however, another mutation, involving a W to L or K substitution at Mpl codon 515, was reported in a small proportion of adult ET patients that is extremely rare in children. Herein, we describe a Mpl W515K somatic mutation in a paediatric case of ET who presented with Budd-Chiari syndrome. No paediatric patient harbouring a Mpl W515K mutation has been previously reported.

An autoimmune disease refractory to immunosuppressive regimens: celiac disease diagnosed long after liver transplantation.

CD is defined as T-lymphocyte-mediated gluten sensitivity. Although CD is known to affect the small intestine, it is nonetheless a multisystem disorder. Liver involvement in CD may vary from isolated hypertransaminasemia to cirrhosis. Because CD is an inappropriate immune response to gluten proteins, strict gluten-free diet is the principal therapy, along with management of liver dysfunction. In patients who fail to respond to a gluten-free diet, immunosuppressive drugs may improve intestinal inflammatory activity in untreated CD. The present case report is of a 25-yr-old woman with diarrhea lasting several weeks. The patient had received a liver transplant 13 yr earlier, and presented with cryptogenic cirrhosis diagnosed as CD. This appears to be the first case of its kind in which a pediatric long-term liver transplant patient presents with diarrhea eventually diagnosed as CD whose diet included gluten, and who was treated by an immunosuppressive drug regimen. Because of the normalization of CD-related antibodies in the post-transplantation period without gluten restriction, CD should be part of a list of diagnostic possibilities in liver transplant patients presenting with diarrhea of unknown etiology.

Evaluation of nutritional status and related factors in children with cystic fibrosis.

BACKGROUND: This study aimed to evaluate the nutritional status and body composition in children with cystic fibrosis (CF), in accordance with the new nutritional targets defined by European Society for Clinical Nutrition and Metabolism (ESPEN), the European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) and the European Cystic Fibrosis Society (ECFS) 2016. METHODS: In this cross-sectional study, data were collected prospectively in a single centre. A record was made for a total of 95 patients with CF of clinical data. Anthropometric data were evaluated using the World Health Organization growth standards. The bone mineral density (BMD) z-score was adjusted for height by measuring dual-energy X-ray absorptiometry (DXA). The speed of sound z-score values were measured with quantitative ultrasound (QUS). RESULTS: The nutritional status was normal in 37.9% of patients aged < 2 years and 33.3% of patients aged 2-18 years. When the DXA BMD z-score values were corrected for height, it was determined that the BMD deficit was less. The calcaneus QUS SOS z-score mean value was lower than the mean height for age z-score adjusted BMD (BMDHAZ). CONCLUSIONS: The malnutrition rates of CF patients were higher than the rates previously reported in literature. As there are insufficient nutritional data in Turkey, there is a need for multi-centre studies to determine the frequency of malnutrition according to the new classifications. It is clear that QUS measurements cannot replace DXA in the diagnosis of osteopenic bone disease. However, when low values are determined with QUS as the first recommended measurement in the screening of bone status, it can be considered appropriate to confirm the status with DXA.

Nutritional characteristic of children with inflammatory bowel disease in the nationwide inflammatory bowel disease registry from the Mediterranean region.

BACKGROUND/OBJECTIVES: We analyzed the nationwide pediatric inflammatory bowel disease (PIBD) registry (1998-2016), to evaluate the nutritional status at the time of diagnosis. SUBJECTS/METHODS: Nine types of nutritional status by the combination of weight-for-length (<2 years)/body mass index (>2 years) and length/height-for-age with three categories (<-2, -2 to 2, and >2 SD) were described. Malnutrition was defined by WHO criteria. Univariate and multivariate regression analysis was used to identify risk factors for malnutrition. RESULTS: In total, 824 IBD patients (498 Ulcerative colitis (UC); 289 Crohn's Disease (CD); 37 Indeterminate Colitis (IC); 412 male; the median age 12.5 years) were eligible. The prevalence of eutrophy, wasting/thinness, stunting, overweight, tall stature, concurrent wasting/thinness and stunting, tall stature with overweight, tall stature with wasting/thinness, and short stature with overweight were 67.4%, 14.9%, 6.6%, 3.1%, 3.2%, 3.3%, 1.1%, 0.4%, and 0.1%, respectively. The prevalence of malnutrition was 32.7%, indicating a higher prevalence in CD (p < 0.001). Incidence of overweight was less common in the CD than UC and IC (p < 0.001). Multivariate analysis revealed that age of onset (>10 years), prepubertal stage, severe disease activity, perianal involvement, and high C reactive protein level were independently associated with malnutrition in pediatric IBD. CONCLUSION: We showed the frequency of nutritional impairment in PIBD. The percentage of overweight subjects was lower than the other studies. The age of onset, disease activity, CRP level, perianal involvement, and pubertal stage were associated with a higher risk for developing malnutrition. Our results also confirmed that CD patients are particularly vulnerable to nutritional impairment. CLINICAL TRIAL NUMBER: ClinicalTrials.gov Identifier: NCT04457518.

Late-onset graft-versus-host disease after pediatric living-related liver transplantation for Langerhans cell histiocytosis.

GVHD is the most common and well-known cause of morbidity and mortality following allogeneic BM transplantation. The GVHD following OLT is an uncommon complication but has a high mortality and poses a major diagnostic and therapeutic challenge. We herein discussed a 12-month-old girl with multi-system LCH, who developed end-stage liver disease despite intensive chemotherapy. She underwent ABO-compatible liver transplantation at 28 months while in remission from LCH. The donor was her 26-yr-old father. Post-operative course was uneventful. The GVHD manifested with skin rash and BM suppression on post-transplant day 94 and confirmed by both microchimerism and skin biopsy. Prednisolone, basiliximab, and ATG were administered immediately but the bone marrow suppression was not improved and the patient died because of Candida sepsis at six-month post-transplant. GVHD after OLT should be keep in mind in patients with rash and BM suppression after liver transplantation. In LDLT, a patient who carries risk factors should investigated for optimal HLA matching.

Evaluation of growth after liver transplantation in Turkish children.

AIMS: Currently, the main interest in childhood liver transplantation (LT) is to prevent long-term complications and optimize growth. The aim of this study is to analyze (1) nutritional status in the pretransplantation period, and (2) posttransplantation growth and associated factors in children. PATIENTS AND METHODS: Eighty children were included in the study. Height (Z (H)) and weight (Z (W)) Z scores were calculated before transplantation and postoperatively at the 6th month and 1st, 2nd, 3rd, 4th, and 5th year. RESULTS: Patients' Z (H) and Z (W) scores at LT were -1.6 ± 1.3 and -1.5 ± 1.4, respectively. Both Z (H) and Z (W) scores increased after LT, especially in the first 6 months, and then continued to rise gradually. Both reached beyond -1 Z score at 2nd year and -0.5 at 4th year. Age, primary diagnosis, total steroid dose (<1,000 mg), and absence of rejection episodes had positive impact on posttransplantation growth, whereas gender, immunosuppression type, surgical complications, and presence of tumor had no impact on posttransplantation growth. Age at time of LT was negatively correlated with Z (W) score at 5th year (P = 0.02, r = -0.43). Both Z (W) and Z (H) scores at time of LT were positively correlated with Z (W) and Z (H) scores and negatively correlated with ∆Z (W) and ∆Z (H) scores at 5th year. CONCLUSIONS: LT is not only a modern, life-saving treatment technique but also an efficient method of facilitating growth, an indispensable component of childhood and the best indicator of health.

Familial Mediterranean Fever Mutation Analysis in Pediatric Patients With Inflammatory Bowel Disease: A Multicenter Study.

BACKGROUND: The aim of the study was to evaluate familial Mediterranean fever (FMF) mutation analysis in pediatric patients with inflammatory bowel disease (IBD). The relation between MEFV mutations and chronic inflammatory diseases has been reported previously. METHODS: Children with IBD (334 ulcerative colitis (UC), 224 Crohn's disease (CD), 39 indeterminate colitis (IC)) were tested for FMF mutations in this multicenter study. The distribution of mutations according to disease type, histopathological findings, and disease activity indexes was determined. RESULTS: A total of 597 children (mean age: 10.8 ± 4.6 years, M/F: 1.05) with IBD were included in the study. In this study, 41.9% of the patients had FMF mutations. E148Q was the most common mutation in UC and CD, and M694V in IC (30.5%, 34.5%, 47.1%, respectively). There was a significant difference in terms of endoscopic and histopathological findings according to mutation types (homozygous/ heterozygous) in patients with UC (P < .05). There was a statistically significant difference between colonoscopy findings in patients with or without mutations (P = .031, P = .045, respectively). The patients with UC who had mutations had lower Pediatric Ulcerative Colitis Activity Index (PUCAI) scores than the patients without mutations (P = .007). CONCLUSION: Although FMF mutations are unrelated to CD patients, but observed in UC patients with low PUCAI scores, it was established that mutations do not have a high impact on inflammatory response and clinical outcome of the disease.

Successful treatment of a child having generalized Kaposi's sarcoma after living donor liver transplantation with conversion to sirolimus.

SRL is a new and potent immunosuppressive agent that has been successfully introduced in organ transplantation. In contrast to other immunosuppressive agents, SRL has a potent antitumor activity both in vitro and in vivo. Herein, we report a child with Kaposi's sarcoma that was diagnosed 30 months after LDLT and treated successfully with only conversion to SRL monotherapy. KS regressed completely at the end of the first month and remained in remission during 28 months follow-up.

Impact of liver transplantation on rate-corrected QT interval and myocardial function in children with chronic liver disease*.

Prolonged QTc interval (>440 ms) is a common abnormality in adult patients with CLD and has been reported to predict patient survival. In this study, 88 children who underwent evaluation for LT, including a 12-lead electrocardiogram and echocardiogram included to determine the frequency of QTc prolongation and related factors in children with CLD and the effect of LT on these factors. Sixty-nine healthy, age- and sex-matched children served as controls. QTc interval was prolonged in 40 CLD patients (45.4%). It was found to be related to PELD score and presence of portal hypertension. Mean QTc was higher in patients who died prior to LT than in the survivors without LT. Mortality risk was increased 3.66-fold in patients with prolonged QTc (p = 0.001, 95% CI: 2-7.2). Cox regression analysis showed that only PELD score was an independent predictor of survival (p = 0.001, beta = -0.41, 95% CI: 5.58-1.82). Five of 48 transplanted children died within three months post-transplant; QTc was not related to post-transplant survival (p = 0.27). QTc normalized in 63.8% patients after LT. After LT, LAD, LVEF, and LVPWT decreased. In conclusion, QTc prolongation is common in children with CLD and associated with high mortality. It may be useful for assessment of the severity of CLD and for the timing for transplantation.

Liver transplantation for acute liver failure due to toxic agent ingestion in children.

ALF is characterized by sudden onset, impaired liver function, jaundice and encephalopathy, without previous liver disease. We analyzed the patients who underwent LT due to toxic agent induced ALF to raise community awareness about preventing the toxic agent induced ALF. Five children (three boys, two girls) underwent LT due to toxic agent ingestion. Toxic agents were mushroom poisoning (n = 2), Datura stramonium (n = 1), yellow phosphorous (n = 1) and INH (n = 1). On admission, one patient had stage IV, two had stage III and two had stage II hepatic encephalopathy but worsened during the follow-up. One patient had renal failure, and three patients required mechanical ventilation. Three patients underwent LRLT and others from a DD. Post-operative complications were managed by supportive managements successfully, and overall all the patients are alive (100% survival) without any organ sequelae. Although outcome of these patients are excellent, ALF may be prevented in these cases by educating the public about consuming mushrooms and toxic effects of wild plants, prohibiting fireworks and serial liver enzyme measurements after initiating INH.

Long-term effect of gluten-free diet on growth velocity in Turkish children with celiac disease.

We sought to analyze the long-term growth in children with celiac disease (CD) as well as the association of height and weight SD score at the end of 4 years with the demographic and clinical presentation at initial admission. Thirty-four children with CD were enrolled in the study and followed for at least 4 years. Patients were divided into three groups (Group 1: patients 10 years, at the time of diagnosis). Patients' charts were reviewed for demographic and clinical features at initial admission. Anthropometric measurements at initial admission, at 6th months, and 1st, 2nd, 3rd, and 4th years were recorded. Gluten-free diet led to rapid increase in weight SD and height SD score in patients

Foreign body ingestion in Turkish children.

Foreign body ingestion (FBI) is a common problem in the pediatric population. Even though morbidity and mortality due to foreign body ingestion are rare in childhood, they may cause serious anxiety in parents. We aimed to analyze the clinical presentation, etiology and management strategy of FBI in children in our country. Records of children admitting with a history of FBI over a three-year period were reviewed retrospectively. Data regarding gender, age, type of the ingested body, management strategy and outcome of the patients were recorded. Of 176 children, 98 (55.6%) were male. Mean age +/- SD of the patients was 3.75 +/- 4.25 years, and most of the patients were below four years of age (71.5%). Most of the children (64.7%) were seen within 48 hours, and most were asymptomatic. Blue beads attached to a safety pin (a cultural good luck charm) (38.6%), coins (27.8%) and turban pins (18.1%) were the most commonly observed foreign bodies. The blue beads/safety pin were found to be ingested primarily by infants, while ingestion of turban pins was mostly seen in adolescent girls who covered their heads. Localization of the foreign bodies was in the distal small intestine, stomach and esophagus in 61.4%, 23.8% and 14.7% of the cases, respectively. Sixty-nine endoscopic interventions were performed in 61 patients (34.6%), and these accounted for 7.3% of all endoscopic interventions during the three-year period. No major complication was observed during the procedure, and none of the patients underwent surgery. The frequently used accessory devices were retrieval net basket (57.9%), snare for pins (17.3%), tripod forceps and rat-tooth forceps. The blue beads/safety pin and turban pin were the commonly ingested foreign bodies in our center due to cultural factors. Education of the parents and of adolescent girls should greatly reduce the incidence of FBI. Endoscopic removal is safe without any major complications.

Chronic constipation in Turkish children: clinical findings and applicability of classification criteria.

We aimed to evaluate general features of children with chronic constipation and classified them according to the Iowa criteria and Rome II criteria in order to analyze applicability of these criteria in our population. The medical records of 485 children who were referred for chronic constipation over a six-year period were evaluated retrospectively. We found that 7.7% of the cases had an organic pathology, and short segment Hirschsprung disease was the leading cause. Other children (92.3%) were classified as functional constipation, with a mean age of 6.4 +/- 4 years and with slight male dominance. Encopresis was found in 117 children (51.7%) aged over four years, and was associated with older age, male predominance and long duration of symptoms. Both of the classification systems showed a similar prevalence of constipation, but 9.9% of the children with pediatric constipation were not recognized by Rome II criteria. Additionally, 1.8% of the children were not recognized by either Iowa or Rome criteria. Functional constipation is common in primary care, and most of the children were school-aged. Constipation associated with encopresis and nutritional problems such as obesity is less common in developing countries. Rome II criteria are too restrictive and do not recognize approximately 12% of the children. A new classification system must be simple, easy to understand especially by the primary care physician, and must include the common features of constipation recognized by the parents.

Timing of Roux-en-Y limb reconstruction for pediatric live donor liver transplantation.

BACKGROUND: Roux-en-Y (R-Y) hepaticojejunostomy is usually accepted as the standard method of choice for biliary reconstruction in pediatric cases though the potential risks for gastrointestinal complications are higher. In this study, we examined gastrointestinal complications in pediatric patients by comparing two different strategies of R-Y reconstruction with respect to the portal clampage time. METHODS: Forty-three pediatric recipients who underwent Live Donor Liver Transplantation with R-Y for biliary reconstruction between March 2001 and December 2006 in our transplantation center were divided into two groups regarding the time of dissection and creation of the roux limb. R-Y limb reconstruction was performed before clampage of the portal vein in group A-preclampage group. In group B, because of prolonged catheterization period, R-Y limb was reconstructed after implantation of the graft (Group B- postclampage group). RESULTS: Overall, seven patients (16%) had gastrointestinal bleeding in the postoperative period, all in group B (0/20 vs. 7/23, P<0.01). One of those three cases who were diagnosed after endoscopy and one another were performed surgical treatment. Although remaining three cases had multiple bleeding episodes but no diagnostic findings by endoscopic/colonoscopic interventions, conservative treatment was successful and therefore, plausible R-Y limb bleeding was considered for these cases. The timing of removal of nasogastric tube and postoperative oral intake were also significantly earlier (P<0.01) in Group A than in Group B. CONCLUSION: In Live Donor Liver Transplantation, if recipient team may have enough time until the donor team got ready for the recovery of the graft, dissection and preparation of the R-Y limb should be performed. This approach can be helpful to avoid gastrointestinal complications due to the reconstruction of the R-Y limb.

Helicobacter pylori infection in children with celiac disease.

OBJECTIVE: To analyze the prevalence of Helicobacter pylori (H. pylori) infection in children with celiac disease (CD) and to examine the role of H. pylori infection in clinical, laboratory and histopathological presentations of CD. MATERIAL AND METHODS: Data on 96 children with CD and 235 children who underwent endoscopy were compared for the prevalence and gastric histology pattern of H. pylori. Clinical presentation, laboratory and histological findings of CD children with and without H. pylori infection were compared. RESULTS: Twenty-one subjects (21.8%) in the CD group and 56 subjects (23.8%) in the control group had H. pylori gastritis. Gastric metaplasia is higher in CD patients with H. pylori gastritis (19%) than in patients without H. pylori gastritis (1.3%) and in the control group (3.5%) (p<0.05 for all groups). Abdominal distension is more common at initial admission in CD patients with H. pylori gastritis (57.1% versus 14.6%, p<0.05). No significant difference was found between H. pylori (+) and (-) CD patients in terms of prevalence of anemia, iron deficiency and iron-deficiency anemia. Only mild duodenal histological findings were more common in H. pylori patients (57.1% versus 26.7%, p<0.05). CONCLUSIONS: CD may be associated with H. pylori gastritis, but it does not affect the clinical presentation of the disease, except for abdominal distension; CD is associated with mild duodenal lesions. A gluten-free diet improves the symptoms in all patients independently of the presence of H. pylori gastritis. Gastric metaplasia increases in the presence of H. pylori gastritis. Further prospective studies are needed to examine the clinical and histopathological outcomes of gastric metaplasia associated with H. pylori gastritis in CD patients.